1. Field of the Invention
The present invention relates to compositions for the treatment of preterm infants. The present invention also relates to methods for reducing the pulmonary oxidative damages and the risk of developing bronchopulmonary dysplasia in preterm infants.
2. Discussion of the Background
The human lung consists of a large number of small air sacs, called alveoli, in which gases are exchanged between the blood and the air spaces of the lungs. In healthy individuals, this exchange is mediated by the presence of a protein-containing surfactant complex that prevents the lungs from collapsing at the end of expiration.
The lung surfactant complex is primarily composed of lipid and contains minor amounts of various proteins. An absence of adequate levels of this complex results in malfunction of the lungs. This syndrome is called Respiratory Distress Syndrome (RDS), and it commonly affects preterm infants.
The mainstay of the treatment of RDS is the replacement therapy with exogenous pulmonary surfactant preparations. Exogenous pulmonary surfactants are currently administered by endotracheal instillation as a suspension in a saline aqueous solution to intubated pre-term infants kept under mechanical ventilation with oxygen.
Although said therapy has greatly increased postnatal survival, children surviving RDS have a high risk of developing bronchopulmonary dysplasia (BPD), a complication impairing lung development and ultimately leading to impaired breathing. Evidence indicates oxidative injuries of lung tissues play an important role in the pathogenesis of BPD and that the reduced antioxidant enzymes activities during hyperoxia result in increased susceptibility to bronchopulmonary dysplasia.
To counteract the effects of reactive oxygen species, it has been proposed to supplement surfactant preparations with antioxidant enzymes, such as superoxide dismutase and catalase, which are often deficient in the premature lung. However, so far, no indications have been provided regarding the therapeutically effective dose of said enzymes in humans without altering the surface activity of the surfactant or causing other side effects. For instance, it has been reported that scavenging of reactive oxygen species by superoxide dismutase may compromise the phagocytic bactericidal activity.
There is therefore still a need to develop a safe medicament effectively reducing the markers of oxidative stress, and hence the risk of BPD in infants suffering from RDS.